EFFECTS OF ALL-TRANS RETINOIC ACID AND RETINOIDS ON ANGIOGENESIS
| Project/Area Number |
18591015
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Endocrinology
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| Research Institution | Tohoku University |
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Principal Investigator |
SUGAWARA Akira Tohoku University, TOHOKU UNIVERSITY GRADUATE SCHOOL OF MEDICINE, PROFESSOR (90270834)
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| Co-Investigator(Kenkyū-buntansha) |
ITO Sadayoshi TOHOKU UNIVERSITY GRADUATE SCHOOL OF MEDICINE, 大学院・医学系研究科, PROFESSOR (40271613)
SATO Yasufumi TOHOKU UNIVERSITY INSTITUTE OF DEVELOPMENT, AGING AND CANCER, PROFESSOR (50178779)
KAGECHIKA Hiroyuki TOKYO MEDICAL AND DENTAL UNIVERSITY, SCHOOL OF BIOMEDICAL SCIENCE, PROFESSOR (20177348)
SATO Akira TOHOKU UNIVERSITY, GRADUATE SCHOOL OF MEDICINE, LECTURER (20250764)
宇留野 晃 東北大学, 病院・医員 (90396474)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥3,790,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥390,000)
Fiscal Year 2007: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2006: ¥2,100,000 (Direct Cost: ¥2,100,000)
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| Keywords | all-trans retinoic acid / retinoic acid receptor / angiogenesis / retinoid / endothelial cells / all-trans retinoic acid / retinoic acid receptor / angiogenesis / retinoid / endothelial cells / 血管内皮増殖因子 / 動脈硬化 / 受容体 |
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| Research Abstract |
A natural retinoid all-trans retinoic acid (ATRA) regulates a variety of important cellular functions via retinoic acid receptor (RAR). ATRA has therapeutically been utilized against various malignancies including acute promyelocytic leukemia. Recently, ATRA has also been recognized to be beneficial against atherosclerotic vascular disorders. However, its effects on angiogenesis remain controversial. We therefore examined ATRA effects on in vitro angiogenesis in terms of capillary-like tube formation using human umbilical vein endothelial cells (HUVEC)/normal human dermal fibroblasts (NHDF) co-culture. ATRA as well as RAR agonist Am80 significantly induced capillary-like tube formation. The ATRA-induced tube formation was inhibited by co-incubation with RAR antagonist LE540/LE135. HUVEC proliferation, but not its migration, was also induced by ATRA. The ATRA-induced tube formation was completely abolished by co-incubation with vascular endothelial growth factor (VEGF) neutralizing antibody or with VEGF receptor (VEGFR)-2 (KDR) neutralizing antibody, but not with VEGFR-1 (Flt-1) neutralizing antibody. ATRA and Am80 induced VEGF gene promoter in NHDF was stimulated by ATRA, which was augmented by RAR overexpression. ATRA also induced VDGFR-2/KDR mRNA expression in HUVEC. Moreover, ATRA induced secretion of hepatocyte growth factor (HGF) as well as angiopoietin-2 (Ang-2) in the co-culture. Taken together, ATRA may have induced angiogenesis via RAR mainly by stimulation of HUVEC proliferation and enhancement of endogenous VEGF signaling, and in part by induction of HGF and Ang-2 production. Retinoids may therefore be potential candiadates for therapeutic angiogenesis against ischemic vascular disorders.
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Report
(3 results)
Research Products
(170 results)
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[Journal Article] All-trans retinoic acid induces in vitro angiogenesis via retinoic acid receptor: possible involvement of endogenous vascular endothelial growth factor signaling.2007
Author(s)
Saito A, Sugawara A, Uruno A, Kudo M, Kagechika H, Sato Y, Owada Y, Kondo H, Sato M, Kurabayashi M, Imaizumi M, Tsuchiya S, Ito S
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Journal Title
Endocrinology 148
Pages: 1412-1423
Description
「研究成果報告書概要(和文)」より
Related Report
Peer Reviewed
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[Journal Article] All-trans retinoic acid induces in vitro angiogenesis via retinoic acid receptor: possible involvement of endogenous vascular endothelial growth factor signaling2007
Author(s)
Saito A, Sugawara A, Uruno A, Kudo M, Kagechika H, Sato Y, Owada Y, Kondo H, Sato M, Kurabayashi M, Imaizumi M, Tsuchiya S, Ito S.
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Journal Title
Endocrinology 148
Pages: 1412-1423
Description
「研究成果報告書概要(欧文)」より
Related Report
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[Journal Article] All-trans retinoic acid induces in vitro angiogenesis viaretinoic acid receptor : possible involvement of endogenous vascular endothelial growth factor signaling.2007
Author(s)
Saito A, Sugawara A, Uruno A, Kudo M, Kagechika H, Sato Y, Owada Y, Kondo H, Sato M, Kurabayashi M, Imaizumi M, Tsuchiya S, Ito S
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Journal Title
Endocrinology 148
Pages: 1412-1423
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[Presentation] Reduced β-cell proliferation and impaired glucose tolerance in pancreatic β-cell specific Extl3 knockout mice2007
Author(s)
Takahashi I, Nata K, Noguchi N, Ikeda T, YoshikawaT, Yamauchi A, Shervani NJ, Sugihara K, Asano M, Uruno A, Unno M, Takasawa S, Okamoto H, Sugawara A
Organizer
80th Annual Meeting of the Japanese Biochemical Society
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Year and Date
2007-12-13
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Organizer
80th Annual Meeting of the Japanese Biochemical Society
Place of Presentation
Yokohama
Year and Date
2007-12-12
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Author(s)
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Organizer
第39回日本医学教育学会大会
Place of Presentation
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Year and Date
2007-07-28
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金村政輝、菅原 明, 石井誠一, 木村秀樹, 小笠原博信, 溝口二郎, 金塚 完, 伊藤恒敏, 本郷道夫
Organizer
第39回日本医学教育学会大会
Place of Presentation
盛岡
Year and Date
2007-07-27
Description
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[Presentation] Impaired beta-cell replication in heterozygous mutant mice of Reg receptor gene.2007
Author(s)
Takasawa S, Nata K, Takahashi I, Ikeda T, Noguchi N, Yamauchi A, Yoshikawa T, Shervani NJ, Sugihara K, Asano M, Unno M, Sugawara A, Okamoto H
Organizer
American Diabetes Association 67th Scientific Sessions
Place of Presentation
Chicago
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[Presentation] Embryonic lethality and impaired beta-cell replication by disruption of Reg receptor gene.2007
Author(s)
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Organizer
43rd Annual Meeting of the European Association for the Study of Diabetes
Place of Presentation
Amsterdam
Description
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[Presentation] Impaired beta-cell replication in heterozygous mutant mice of Reg receptor gene2007
Author(s)
Takasawa S, Nata K, Takahashi I, Ikeda T, Noguchi N, Yamauchi A, Yoshikawa T, Shervani NJ, Sugihara K, Asano M, Unno M, Sugawara A, Okamoto H
Organizer
American Diabetes Association 67^<th> Scientific Sessions
Place of Presentation
Chicago
Description
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[Presentation] Embryonic lethality and impaired beta-cell replication by disruption of Reg receptor gene2007
Author(s)
Takasawa S, Nata K, Takahashi I, Ikeda T, Noguchi N, Sugihara K, Asano M, Yamauchi A, Yoshikawa T, Shervani NJ, Unno M, Sugawara A, Okamoto H
Organizer
43rd Annual Meeting of the European Association for the Study of Diabetes
Place of Presentation
Amsterdam
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Author(s)
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Organizer
44th Regional Meeting of Japan Diabetes Society
Place of Presentation
Sendai
Year and Date
2006-11-04
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[Presentation] 医療面接教育実習効果の評価。2006
Author(s)
長崎 裕、菅原 明、金塚 完、本郷道夫
Organizer
第38回日本医学教育学会大会
Place of Presentation
奈良
Year and Date
2006-07-30
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Year and Date
2006-07-30
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Place of Presentation
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Year and Date
2006-07-29
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Organizer
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Place of Presentation
Nagoya
Year and Date
2006-07-08
Description
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[Presentation] Effects of ATRA on angiogenesis2006
Author(s)
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Organizer
12th Tohoku Endocrine Meeting
Place of Presentation
Sendai
Year and Date
2006-04-08
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[Presentation] Analyses of diabetes patients Who admitted to Tohoku Univ. Hosp. Dept. of Comp. Med.2006
Author(s)
Sugawara A, Gomi R, Kanatsuka H, Nagasaki Y, Ogawa S, Hinokio Y, Suzuki S, Katagiri H, Ito S, Oka Y, Hongo M
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Place of Presentation
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[Presentation] Effects of ATRA on angiogenesis2006
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Organizer
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